Digital twin for lyophilization by process modeling in manufacturing of biologics

Abstract

Lyophilization stabilizes formulated biologics for storage, transport and application to patients. In process design and operation it is the link between downstream processing and with final formulation to fill and finish. Recent activities in Quality by Design (QbD) have resulted in approaches by regulatory authorities and the need to include Process Analytical Technology (PAT) tools. An approach is outlined to validate a predictive physical‐chemical (rigorous) lyophilization process model to act quantitatively as a digital twin in order to allow accelerated process design by modeling and to further‐on develop autonomous process optimization and control towards real time release testing. Antibody manufacturing is chosen as a typical example for actual biologics needs. Literature is reviewed and the presented procedure is exemplified to quantitatively and consistently validate the physical‐chemical process model with aid of an experimental statistical DOE (design of experiments) in pilot scale.